Newly diagnosed multiple myeloma MedDRA version: 18.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Product Name: MLN9708 2.3 mg
Product Code: MLN9708
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ixazomib citrate
CAS Number: 1239908-20-3
Other descriptive name: MLN9708
Concentration unit:
Sponsors
Millennium Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult male or female patients 18 years old and above with a confirmed diagnosis of symptomatic multiple myeloma according to standard criteria who have not received prior treatment for symptomatic multiple myeloma 2. Patients for whom lenalidomide and dexamethasone treatment is appropriate and who are not eligible for HDT-SCT for 1 or more of the following reasons: * The patient is 65 years of age or older * The patient is less than 65 years of age but has significant comorbid condition(s) that are, in the opinion of the investigator, likely to have a negative impact on tolerability of HDT-SCT 3. Patients must have measurable disease defined by at least 1 of the following 3 measurements: * Serum M-protein = 1 g/dL (= 10 g/L) * Urine M-protein = 200 mg/24 hours * Serum free light chain assay: involved free light chain level = 10 mg/dL (= 100 mg/L), provided that the serum free light chain ratio is abnormal 4. Patients must meet the following clinical laboratory criteria: * Absolute neutrophil count (ANC) = 1,000/mm3 and platelet count = 75,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days prior to randomization * Total bilirubin = 1.5 × the upper limit of the normal range (ULN). * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 × ULN. * Calculated creatinine clearance = 30 mL/min NOTE: Patients with a low creatinine clearance = 60 mL/min (or = 50 mL/min, according to local label/practice) will receive a reduced lenalidomide dose of 10 mg once daily on Days 1 through 21 of a 28-day cycle. The lenalidomide dose may be escalated to 15 mg once daily after 2 cycles if the patient is not responding to treatment and is tolerating the treatment. If renal function normalizes (ie, creatinine clearance > 60 mL/min or > 50 mL/min, according to local label/practice) and the patient continues to tolerate this treatment, lenalidomide may then be escalated to 25 mg once daily. 5. ECOG performance status of 0, 1, or 2. 6. Female patients who: * Are postmenopausal for at least 24 months before the screening visit, OR * Are surgically sterile, OR * Females of childbearing potential (FCBP) must: a. US and European Union (EU): Have TWO medically-supervised negative pregnancy tests (serum or urine with sensitivity of at least 25 mIU/mL), even if continuous abstinence is the chosen method of contraception. One test must be obtained within 10 to 14 days and the other test must be obtained within 24 hours prior to administering the first dose of the study drug regimen at Cycle 1, Day 1. The dates and results of pregnancy tests must be documented c. Either agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient (periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception) OR begin TWO reliable methods of birth control: 1 highly effective method and 1 additional effective method AT THE SAME TIME, at least 28 days before starting the study drug regimen through 90 days after the last dose of study treatment d. Agree to ongoing pregnancy testing e. Adhere to the guidelines of the The Lenalidomide Pregnancy Risk Minimisation Plan as outlined in the Study Manual (all other participants who are not using commercial supplies) Male patients, even if surgically sterilized (ie, status postvasectomy), must: * Agree to prac
Exclusion criteria
Exclusion criteria: 1. Prior treatment for multiple myeloma with either standard of care treatment or investigational regimen NOTE: Prior treatment with corticosteroids or localized radiation is permitted as long as it is below a therapeutic level (maximum dose of corticosteroids should not exceed the equivalent of 160 mg of dexamethasone over a 2-week period) 2. Radiotherapy within 14 days before randomization 3. Diagnosed and treated for another malignancy within 5 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection 4. Inability or unwillingness to receive antithrombotic therapy 5. Female patients who are lactating and breastfeeding or have a positive pregnancy test during the screening period 6. Major surgery within 14 days before randomization. NOTE: Kyphoplasty or vertebroplasty is not considered major surgery 7. Central nervous system involvement 8. Infection requiring IV antibiotic therapy or other serious infection within 14 days before randomization 9. Diagnosis of Waldenstrom’s macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome. 10. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months 11. Systemic treatment with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John’s wort within 14 days before randomization in the study 12. Active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive. 13. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens (eg, peripheral neuropathy that is Grade 1 with pain or Grade 2 or higher of any cause). 14. Psychiatric illness/social situation that would limit compliance with study requirements 15. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent 16. Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or gastrointestinal (GI) procedure that could interfere with the oral absorption or tolerance of treatment 17. Treatment with any investigational products within 60 days before the first dose of the study drug regimen
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether the addition of oral MLN9708 to lenalidomide and dexamethasone improves progression-free survival (PFS) in patients with newly-diagnosed multiple myeloma (NDMM);Secondary Objective: * To determine whether the addition of oral MLN9708 to lenalidomide and dexamethasone improves the rate of complete response (CR) * To determine whether the addition of oral MLN9708 to lenalidomide and dexamethasone improves overall survival (OS) * To determine whether the addition of oral MLN9708 to lenalidomide and dexamethasone improves pain response rate, as assessed by the Brief Pain Inventory – Short Form (BPI-SF) and analgesic use;Primary end point(s): PFS, defined as the time from the date of randomization to the date of first documentation of disease progression based on central laboratory results and IMWG criteria as evaluated by an IRC, or death due to any cause, whichever occurs first.;Timepoint(s) of evaluation of this end point: SPEP, UPEP and chemistry laboratory assessments will be performed at screening, day 1 of every cycle, end of treatment, and every 4 weeks during PFS follow-up period. Skeletal survey will be performed at screening and a minimum of every 12 months until disease progression for all patients. More frequent skeletal survey can be done at the discretion of the investigator. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. CR rate during the treatment period 2. OS, measured as the time from the date of randomization to the date of death 3. Pain response rate, measured by the proportion of pain responders, as determined by BPI-SF and analgesic use;Timepoint(s) of evaluation of this end point: 1. Bone marrow aspirate at screening for disease assessment. Repeated when deemed necessary to assess CR or to investigate suspected PD. Radiographic disease assessment for patients with extramedullary disease at screening, day 1 of every other cycle during treatment, and every 8 weeks during the PFS follow-up period until disease progression. 2. Follow-up for survival in the OS follow-up period (patients contacted every 12 weeks until death or termination of the study by the sponsor). 3. Pain assessments at screening, day 1 of every cycle, end of treatment, and every 4 weeks during PFS follow-up period. Patients with new or worsening pain between scheduled visits assessed at unscheduled visits, if necessary, or when next scheduled visit is more than 4 weeks in the future. | — |
Countries
Belgium, Canada, France, United States
Contacts
Public ContactMillennium, Drug Information Call C
Millennium Pharmaceuticals, Inc.
Outcome results
None listed